[unreadable] The overall goal of this project is to develop a SPECT system that utilizes pinhole collimators following helical orbits for quantifying radiotracer distributions in small animals. SPECT imaging is an inexpensive technique for in vivo quantification of various compounds in small-animal models of human disease. The system will combine the excellent properties of pinhole collimators for studying small objects, dramatically increasing magnification and sensitivity at small radius of rotation (ROR), with the sampling properties of helical orbits. Circular pinhole orbits do not completely sample the object of interest leading to sampling artifacts in the subsequent reconstructions; the artifacts worsen as the ROR decreases, causing a trade-off between sampling and both sensitivity and magnification. On the other hand, helical orbits of pinhole collimators allow complete sampling with a small ROR resulting in artifact-free reconstructions from projection data acquired at high sensitivity and magnification. The primary goal of the feasibility (R21) phase is the demonstration of artifact-free reconstructions from helical pinhole projection data. Following the feasibility phase, the system will be further developed to provide quantitative radiotracer distributions. Quantitative SPECT will require both attenuation and scatter compensation. A transmission source will be added to the system to determine the object's attenuation map, a necessary component for attenuation compensation. Some scatter compensation algorithms also utilize attenuation maps. The attenuation map will facilitate the development of software and techniques for attenuation and scatter compensation without the added complexity in the initial phase of integrating an x-ray computed tomography (XCT) system. In addition, the parameters of the helical orbit, in conjunction with the aperture parameters, will be investigated to determine their relationship to the quality of reconstructions. Experimental phantoms will be the primary tool used to evaluate the system's ability to quantify the radiotracer distribution. Software simulations and numerical calculations will complement experimental results. In the longer term, it is desirable to upgrade the spiral pinhole SPECT system with an XCT system to replace the transmission source. The XCT system, when combined with the SPECT system, will provide inherently co-registered SPECT/XCT images that will fuse functional information with anatomical information. Another long-term vision for this system is its miniaturization to a table-top research instrument. [unreadable] [unreadable]